Rejected by the New England Journal of Medicine in 2003.

To the Editor:

The Journal’s editorial oversight of Mack’s analysis of smallpox (1) was so flawed that the article should have been presented as medical history, not as a contribution to biodefense policy.

Mack describes “average” smallpox characteristics in naturally occurring outbreaks. This represents a best-case scenario. The next outbreak will not be natural, and it may not be average.

The Soviets, for example, weaponized a highly virulent variola strain (2) and treated their variola “with plastics and resins to increase its potency and longevity in the air” (3). Responsible policy cannot, therefore, assume that attacks will use an average strain and natural delivery of variola.

Mack’s suggestion that “the media should provide more information about the dangers of vaccination” is exactly opposite the true need. In the same issue, Blendon et al (4) report that 25% of Americans believe death is a “likely” outcome of smallpox vaccination. The Journal should have caught the contradiction, and should have used its bully pulpit with lay readers and journalists to provide reminders of the safety of vaccination in appropriate populations.

(1) Mack T. A different view of smallpox and vaccination. N Engl J Med 2003;348:460-3.

(2) Alibek K. Biohazard. New York: Dell Publishing, 1999. Page 112

(3) Statement for the Record by Richard Preston Before The Senate Judiciary Subcommittee on Technology, Terrorism & Government Information and the Senate Select Committee on Intelligence. Chemical and Biological Weapons Threats to America: Are We Prepared? April 22, 1998. Available at: [Link is dead in 2014]

(4) Blendon RJ, DesRoches CM, Benson JM, Herrmann MJ, Taylor-Clark K, Weldon KJ. The public and the smallpox threat. N Engl J Med 2003;348:426-32.

The New England Journal of Medicine rejected this letter in 2001.

To the Editor:

If this were 1903, I would diagnose ochronosis in the woman shown in the April 5 “Medical Mystery” (1). It would be the eighth case in the world’s literature. But if this were 1904, and if I were William Osler (alas!), then I would consider alkaptonuria as an additional diagnosis.

Before 1904, the diagnosis of alkaptonuria applied only to urine. Chemical properties, not color, made the diagnosis. A link with ochronosis had been proposed (2), but Osler was the first to describe ochronosis and alkaptonuria coexisting in patients, thereby bringing alkaptonuria “within the realm of the clinical physician” (3). Today, ochronotic pigmentation is considered a feature of the metabolic disease alkaptonuria (4).

Osler’s paper also lets us ponder the man and his times. Osler describes the examination of his index patient, then states: “As he left the room my attention was directed to the deep blue color of the inner surface of the ears” (3). Even if we were all Oslers (alas!), most physicians are now too busy completing reimbursement forms to watch their patients walk out of the examination room.

(1) Nikkels AF, Pierard GE. Images in clinical medicine. A medical mystery. N Engl J Med. 2001;344:1057.

(2) Albrecht H. Ueber ochronose. Zeitschrift fur Heilkunde. 1902;23:366.

(3) Osler W. Ochronosis: the pigmentation of cartilages, sclerotics, and skin in alkaptonuria. Lancet 1904;i:10-11.

(4) La Du BN. Alkaptonuria. Chapter 39 (pages 1371-1386) in: The Metabolic Basis of Inherited Disease. 7th ed. Scriver CR, Beaudet AL, Sly WS, Valle D (eds). New York: McGraw-Hill, 1995.

The New England Journal of Medicine rejected this letter in 1998.

To the Editor:

Because it emphasized a bedside approach rather than millisecond dissections of electronic catheter tracings, I found Drs. Zimetbaum and Josephson’s discussion of symptoms and circumstances associated with palpitations refreshing (1). They did not mention, however, the tachycardia-polyuria syndrome.

As described in the 1960s, polyuria occurs in approximately half of patients with paroxysmal supraventricular arrhythmias faster than 110 beats per minute lasting for 20 or more minutes when left ventricular failure and stenotic valvular lesions are absent (2,3). Why the syndrome is so underreported to physicians is unclear. Diuresis typically begins 20 to 60 minutes after the onset of the arrhythmia, is most intense in the first 1 to 2 hours, and may last as long as 8 hours if the arrhythmia lasts that long (2,3,4). It is unusual for polyuria to occur before the palpitation or with ventricular arrhythmias.

The syndrome’s physiology is incompletely known, but seems, in part, to depend on a rise in atrial pressure causing release of atrial natriuretic peptides. Of note, in a recent series of 13 patients with atrioventricular nodal reentrant tachycardia (AVNRT), 12 had associated diuresis (5). Compared to other atrial arrhythmias, the rise in atrial pressure was greatest in AVNRT, as might be expected from symptoms typical of this disorder: cannon A waves and a sensation of pounding in the neck (1).

Thus, the tachycardia-polyuria syndrome is probably a useful indicator of a supraventricular tachycardia, and perhaps AVNRT in particular.

(1) Zimetbaum P, Josephson ME. Evaluation of patients with palpitations. N Engl J Med. 1998;338:1369-73.

(2) Wood P. Polyuria in paroxysmal tachycardia and paroxysmal atrial flutter and fibrillation. Br Heart J. 1963;25:273-82.

(3) Luria MH, Adelson EI, Lochaya S. Paroxysmal tachycardia with polyuria. Ann Int Med. 1966;65:461-70.

(4) Zullo MA. Atrial regulation of intravascular volume: observations on the tachycardia-polyuria syndrome. Am Heart J. 1991;122:188-194.

(5) Abe H, Nagamoto T, Kobayashi H, Miura Y, Araki M, Kuroiwa A, Nakashima Y. Neurohumoral and hemodynamic mechanisms during atrioventricular nodal reentrant tachycardia. Pacing Clin Electrophysiol. 1997;20:2783-2788.

Rejected by The Lancet in 1996.
Co-authored with Dr. David Herrington and Dr. Deirdre Herrington.

To the Editor:

Speculations regarding Creutzfeldt-Jakob disease (CJD) acquired from beef containing the infectious agent that causes bovine spongiform encephalopathy [1] have resulted in dramatic health policy measures and serious concerns in the lay public about dietary beef intake in Britain. We believe these concerns are out of proportion to the actual risk of CJD, especially when compared to other established risks of beef consumption, such as the development of coronary heart disease (CHD). We therefore sought to estimate a beef-eater’s risk of CJD and CHD based on currently available data.

The ten cases of CJD became manifest over a 20 month span in 1994-1995 [1]. If we suppose a uniform incubation period of 10 years for CJD, then all 10 cases were infected during a 20 month period in 1984-1985, when the mean beef intake among the 56 million Britons was 181.5 g/person/week [2] (roughly equivalent to two hamburgers per week). Assuming the attack rate remains constant, an average Briton would have a 1 in 933,000 chance of developing CJD from 10 years of beef-eating. The risk per hamburger is roughly 1 in one billion.

To determine the beef-attributable risk of CHD, we first calculate the change in serum cholesterol that results when the fat and cholesterol in lean beef [3] are consumed in place of isocaloric carbohydrate or protein. Using the average daily caloric intake in Britons (2040 kcal) [2], the Hegsted equation [4] predicts a 2.1 mg/dl increase in serum cholesterol when 181.5 g beef/week are consumed. For a 30 year-old non-smoking, non-diabetic man with a total cholesterol of 150 mg/dl, an HDL cholesterol of 45 mg/dl, and a systolic blood pressure of 120 mmHg, the Framingham equation [5] predicts that a 2.1 mg/dl increase in serum cholesterol sustained over 10 years raises the risk of CHD during this period by 1 chance in 5300. Thus the CHD/CJD relative risk is approximately 175!

Although our calculations are approximations at best, they clearly show that the risk from fat and cholesterol in beef is, for most of the adult population, orders of magnitude greater than the risk from neurotropic particles contained therein. Other diseases linked to fat intake, such as stroke and colon cancer, have not been considered here. Based on these data we believe that beef-eaters should care for their coronaries, rather thsn perseverate on prions.

[1] Will RG, Ironside JW, Zeidler, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996;347:921-925.

[2] Ministry of Agriculture, Fisheries and Food. National Food Survey 1994. London: Her Majesty's Stationery Office, 1995.

[3] American Heart Association Cookbook. Ballantine Books. New York, NY, 1986.

[4] Hegsted OM. Serum-cholesterol response to dietary cholesterol: a re-evaluation. Am J Clin Nutr. 1986;44:299-305.

[5] Anderson KM, Wilson PWF, Odell PM, et al. An updated coronary risk profile: a statement for health professionals. Circulation. 1991; 83:356-362.

Dr. Iredell Iglehart and I submitted this letter to the New England Journal of Medicine in early 1987, after reading their report of a supposedly new physical sign using the technique of auscultatory percussion. It was not new. The letter was rejected.

To the Editor:

In a recent letter to the Journal Guarino describes an apparently novel method of detecting ascites: the diaphragm of the stethoscope is placed just superior to the pubic crest of a patient who has been standing for three minutes or more, and the physician determines by auscultation the level where the timbre of the “finger-flicking” percussion note changes from dull to loud (1). A similar technique, alas, was described in the 1930s by two French physicians (2) (3). Without mentioning the three-minute caveat, they found that if the physician auscultated in the iliac fossa of a standing patient with ascites, and percussed the abdomen from superior to inferior, the percussion note had a brusque augmentation at the top of the zone liquidienne (2).

More interestingly, however, the thrust of their articles is directed at a technique they considered far more sensitive and convenient in detecting ascites: listening with the stethoscope bell in one iliac fossa while percussing the contralateral fossa with a “finger pulled back like a hammer” (doigt recourbe en marteau) (3). The presence of ascites is indicated by a distinctive double note in response to percussion (le double bruit ascitique), whereas a single note is heard in normal patients. Abdominal distention due to large ovarian cysts (3) or “enormous urinary retention” (2), the authors say, yields a single sound, while, in cases of hydatidiform cyst, a second sound is present, but of a different character (l’echo hydatique) (2). The authors further claim that, with the patient standing, their method is capable of demonstrating ascites of volume small enough to have otherwise escaped clinical detection. We have ourselves heard the ascitic double note, which the French authors considered the sonic manifestation of a fluid wave (3).

Two hundred years ago, Marie Antoinette’s milliner is reported to have said, “There is nothing new except what is forgotten” (4). The advent of computer-based bibliographic retrieval systems has dramatically improved mankind’s scientific “memory,” but has not perfected it. Thus, there still is (and, most likely, always will be) a vast corpus of pre-electronic knowledge, searchable only by means that are both painful and tedious. Unfortunately, when dealing with an art as ancient as the physical examination, the scrutiny of this literature demands added attention (5).

(1) Guarino JR. Auscultatory percussion to detect ascites. N Engl J Med. 1986 Dec 11;315(24):1555-6.   Pubmed 3785320

(2) Lian C, Odinet J. De l'existence d'un double bruit par la percussion abdominale dans l'ascite. Societe Medicale des Hospitaux de Paris. 1931; 55: 1402-1408.

(3) Lian C, Odinet J. Le double bruit ascitique et le signe de la matite horizontale dans la station debout. Presse Medicale. 1934; 42: 1337-1338.

(4) Bartlett J (comp.). _Familiar Quotations_. 13th ed. Boston: Little, Brown, 1955; 1002.

(5) Sotos JG. Diagnosis of fractures of the hip and pelvis (continued). N Engl J Med. 1983 Apr 21;308(16):971.   Pubmed 6835304